Cigarette smoking and radiographic progression in rheumatoid arthritis.

Background: Smoking is a well-established environmental risk factor for the development of rheumatoid arthritis (RA). However, it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non-smokers over time.

Objective: To compare the rates of radiographic damage progression in current smokers and non-smokers in a large prospective RA cohort.

Remission of collagen-induced arthritis is associated with high levels of transforming growth factor-beta expression in the joint.

Immunization of genetically susceptible strains of mice with heterologous type II collagen leads to the induction of a self-limiting polyarthritis that begins to subside around 10 days after onset of clinical disease. The aims of this study were to compare pro- and anti-inflammatory cytokine expression in the joints during the course of arthritis in order to identify cytokines involved in spontaneous remission of arthritis. DBA/1 mice were immunized with type II collagen and an immunohistochemical analysis of expression of proinflammatory cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6] and anti-inflammatory cytokines [IL-10, IL-1ra, transforming growth factor (TGF)-beta1, TGF-beta2 and TGF-beta3] in joints was carried out over the course of the disease.

The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation.

Interleukin (IL)-1 is a cytokine that plays a major role in inflammatory responses in the context of infections and immune-mediated diseases. IL-1 refers to two different cytokines, termed IL-1alpha and IL-1beta, produced from two genes. IL-1alpha and IL-1beta are produced by different cell types following stimulation by bacterial products, cytokines, and immune complexes.

Systemic rheumatoid vasculitis: a review.

Objectives: To review the most recent information on the incidence, clinical course, pathology, pathogenesis, diagnosis, and treatment of rheumatoid vasculitis (RV), including the still scanty data on the use of biologics.

Methods: PubMed and MEDLINE databases (1950-2006) were searched for the key words "vasculitis" and "rheumatoid arthritis"; and "rheumatoid arthritis" and "extra-articular manifestations." All relevant articles in English and French were reviewed.

Is IL-1 a good therapeutic target in the treatment of arthritis?

Inflammation is an important homeostatic mechanism that limits the effects of infectious agents. However, inflammation might be self-damaging and therefore has to be tightly controlled or even abolished by the organism. Interleukin 1 (IL-1) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of pathological conditions leading to chronic inflammation.

Indirect effects of leptin receptor deficiency on lymphocyte populations and immune response in db/db mice.

Leptin-deficient ob/ob and leptin receptor (Ob-rb)-deficient db/db mice display a marked thymic atrophy and exhibit defective immune responses. Lymphocytes express leptin receptors and leptin exerts direct effects on T cells in vitro. In addition, ob/ob and db/db mice display multiple neuroendocrine and metabolic defects, through which leptin deficiency may indirectly affect the immune system in vivo.

Interleukin-6 and chronic inflammation.

Interleukin (IL)-6 is produced at the site of inflammation and plays a key role in the acute phase response as defined by a variety of clinical and biological features such as the production of acute phase proteins. IL-6 in combination with its soluble receptor sIL-6Ralpha, dictates the transition from acute to chonic inflammation by changing the nature of leucocyte infiltrate (from polymorphonuclear neutrophils to monocyte/macrophages). In addition, IL-6 exerts stimulatory effects on T- and B-cells, thus favoring chronic inflammatory responses.

The role of leptin in innate and adaptive immune responses.

Leptin is produced primarily by adipocytes and functions in a feedback loop regulating body weight. Leptin deficiency results in severe obesity and a variety of endocrine abnormalities in animals and humans. Several studies indicated that leptin plays an important role in immune responses.

The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes.

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8.

[Septic arthritis].

Septic arthritis is a medical emergency that may be associated with significant mortality (10-15%) and morbidity (25-50%), in case of delayed management. When septic arthritis is suspected, arthrocentesis and culture of the synovial fluid are the gold standard. The absence of fever, rigors, leukocytosis or elevated erythrocyte sedimentation rate does not exclude the diagnosis of septic arthritis.

Clinical evaluation of a cohort of patients with rheumatoid arthritis treated with anti-TNF-alpha in the community.

Objectives: TNF-alpha inhibitors have been effective in randomized controlled studies for the treatment of RA. The purpose of this study was to evaluate the clinical, laboratory, and radiological responses in a cohort of unselected patients with RA treated with TNF-alpha inhibitors in the community.

Methods: Using the Swiss Clinical Quality Management in Rheumatoid Arthritis, a centralized system of data gathering for RA patients, we obtained the following information regarding patients treated with a TNF-alpha inhibitor in the Geneva Canton before 02/2003: demographics; clinical data (disease activity, functional status, treatments received and type of TNF-alpha inhibitor used); laboratory and radiographic data.

The effectiveness of anti-tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis: a population-based study.

Objective: To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population-based cohort. The 3 strategies were infliximab with concomitant disease-modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone.

Methods: We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months.

Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis.

Background: Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents.

Objective: To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA).

Methods: Swiss health authorities requested continuous monitoring of patients receiving biological agents.

Intracellular interleukin-1 receptor antagonist type 1 antagonizes the stimulatory effect of interleukin-1 alpha precursor on cell motility.

Interleukin (IL)-1alpha, a proinflammatory cytokine, is produced as a 33 kDa protein precursor (preIL-1alpha) which is cleaved to generate the 17 kDa C-terminal mature IL-1alpha (mIL-1alpha) and the 16kDa N-terminal IL-1alpha propiece (NIL-1alpha). The biological effect of IL-1alpha is regulated by the IL-1 receptor antagonist (IL-1Ra), its naturally occurring inhibitor. Four different isoforms of the IL-1Ra have been described, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3).

Pre-interleukin-1alpha expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: Differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1).

Interleukin-1 receptor antagonist (IL-1Ra) inhibits the classical biological effects of interleukin (IL)-1 by preventing its binding to IL-1 receptors. There are, however, four different isoforms of IL-1Ra, of which three are intracellular (icIL-1Ra1, 2, 3). Due to their localization, icIL-1Ras cannot interact with cell surface IL-1 receptors and have been suggested to carry out specific functions inside cells.

Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice.

Objective: To examine the role of the balance between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1Ra) in atherosclerosis and vascular inflammation.

Methods: Transgenic (Tg) mice overexpressing either secreted IL-1Ra or intracellular IL-1Ra1 as well as IL-1Ra-deficient mice (IL-1Ra -/-) were crossed with apolipoprotein E-deficient mice (ApoE -/-).

Results: In males fed a cholesterol-rich diet for 10 weeks, average atherosclerotic lesion area within aortic roots was significantly decreased in ApoE -/- secreted IL-1Ra Tg (-47%) and ApoE -/- intracellular IL-1Ra1 Tg (-40%) mice as compared to ApoE -/- non-Tg controls.

[Rheumatological arthroscopy].

Arthroscopy is a useful tool for the clinical rheumatologist. It allows the clinician to examine the synovial tissue under direct vision for evidence of active inflammation. It permits tissue sampling.